title: Female-specific hypertension loci on rat chromosome 13.
abstract: A 3.7-Mb region of rat chromosome 13 (45.2-49.0 Mb) affects blood pressure (BP) in females only, indicating the presence of sex-specific BP loci in close proximity to the Renin locus. In the present study, we used a series of Dahl salt-sensitive/Mcwi-13 Brown Norway congenic rat strains to further resolve BP loci within this region. We identified 3 BP loci affecting female rats only, of which the 2 smaller loci (line9BP3 and line9BP4) were functionally characterized by sequence and expression analysis. Compared with SS (SS/HsdMcwiCrl), the presence of a 591-kb region of BN (BN/NHsdMcwi) chromosome 13 (line9BP3) significantly lowered BP by 21 mm Hg on an 8% NaCl diet (153 ± 7 versus 174 ± 5 mm Hg; P<0.001). Unexpectedly, the addition of 23 kb of Brown Norway chromosome 13 (line9BP4) completely erased the female-specific BP protection on 8% NaCl diet, suggesting that BN hypertensive allele(s) reside in this region. The congenic interval of the protective line 9F strain contains 3 genes (Optc, Prelp, and Fmod), and the hypertensive line 9E contains 1 additional gene (Btg2). Sequence analysis of the 2 BP loci revealed a total of 282 intergenic variants, with no coding variants. Analysis of gene expression by quantitative real-time polymerase chain reaction revealed strain- and sex-specific differences in Prelp, Fmod, and Btg2 expression, implicating these as novel candidate genes for female-specific hypertension.
authors.affiliation: Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Hoffman
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Flister
authors.forename: Lizbeth
authors.initials: L
authors.lastname: Nunez
authors.forename: Bing
authors.initials: B
authors.lastname: Xiao
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Greene
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Jacob
authors.forename: Carol
authors.initials: C
authors.lastname: Moreno
mesh_terms: D000483:Alleles; D000818:Animals; D001794:Blood Pressure / Q000235:genetics*; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian; D005260:Female; D056426:Genetic Loci; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D020303:Rats, Inbred Dahl; D012083:Renin / Q000235:genetics
chemical_list: D012083:Renin
keywords: blood pressure; genetics; hypertension; kidney; sex